Research Articles (Medical Microbiology)
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Item Global prevalence, resistance rates, and underlying resistance mechanisms of clinical Mycoplasma and Ureaplasma species(Oxford University Press, 2025-01) Ramaloko, Winnie Thabisa; Maningi, Nontuthuko Excellent; Osei Sekyere, JohnMycoplasmas are significant pathogens in human health, implicated in a range of clinical conditions from respiratory infections to urogenital disorders. Their resistance to commonly used antibiotics poses a substantial challenge to treatment and control. This study aims to provide a comprehensive overview of the global distribution of clinical mycoplasmas, elucidate their resistance to various antibiotics, and identify the genetic and molecular mechanisms underlying their resistance. A systematic review and meta-analysis were conducted, collating data from peer-reviewed publications between 2012 and 2024. The UK (100%) and Germany (98%) reported high numbers of respiratory mycoplasmas, with 7% and 2% being resistant to macrolides. For urogenital mycoplasmas, Iceland (99%) and Estonia (94%) reported a high prevalence of Mycoplasma species, whereas the UK (85%), France (82%), and the USA (82%) reported a high prevalence of Ureaplasma species. High resistance rates in Mycoplasma and Ureaplasma have been reported in Greenland (100%) and the UK (86%), respectively. The rising resistance rates in these species underscore an urgent need for updated treatment guidelines and the development of novel therapeutic options. Our findings highlight the importance of tailored antibiotic stewardship and the potential of genomic insights in guiding effective treatment strategies.Item From pregnancy to beyond : renewed emphasis on comprehensive HIV prevention in South Africa(Lippincott Williams and Wilkins, 2025-03) Babalola, Chibuzor M.; Peters, Remco P.H.; Muzny, Christina A.; Davey, Dvora Joseph; Taylor, Christopher M.; Mdingi, Mandisa M.; Mukomana, Freedom; De Vos, Lindsey; Medina‑Marino, Andrew; Klausner, Jeffrey DSouth Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing “Philani Ndiphile” trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age. National progress toward UNAIDS’ targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum. Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.Item Molecular epidemiology and AMR perspective of diarrhoeagenic Escherichia coli in Africa(Springer, 2024-12) Kalule, John Bosco; Bester, Linda A.; Banda, Daniel L.; Derra, Firehiwot Abera; Msefula, Chisomo; Smith, Anthony M.; Ajayi, Abraham; Kumburu, Happiness; Kwenda, Geoffrey; Yamba, Kaunda; Mwaba, John; Fakim, Yasmina J.; Sithole, Nyasha; Kanzi, Aquillah M.; Njage, Patrick M.K.; Chikuse, Francis; Tessema, Sofonias K.; Smith, Stella I.; Foster‑Nyarko, EbenezerINTRODUCTION : Diarrhoeagenic Escherichia coli (DEC) persistently challenges public health in Africa, contributing substantially to the diarrhoeal disease burden. This systematic review and meta-analysis illuminate the distribution and antimicrobial resistance (AMR) patterns of DEC pathotypes across the continent. METHODS : The review selectively focused on pathotype-specific studies reporting prevalence and/or AMR of human-derived DEC pathotypes from African nations, excluding data from extra-intestinal, animal, and environmental sources and studies focused on drug and mechanism experiments. Pertinent studies were retrieved from SCOPUS, PubMed, and EBSCOhost, processed with Covidence, and screened in alignment with PRISMA guidelines. RESULTS : The reviewed studies were predominantly hospital-based (80%) and paediatric-focused (91%), with a meagre 4.4% documenting DEC outbreaks. Seven DEC pathotypes were discerned, with Enteroaggregative E. coli (EAEC) being notably prevalent (43%, 95% CI 30–55%) and Enteroinvasive E. coli (EIEC) least prevalent (24%, 95% CI 17–32%). Identified nonsusceptibilities were noted against essential antibiotics including ciprofloxacin, ceftriaxone, and ampicillin, while instances of carbapenem and Extended-Spectrum ß-Lactamase (ESBL) resistance were scarce. CONCLUSION : Despite sporadic data on DEC prevalence and AMR in Africa, particularly in community settings, a palpable gap remains in real-time outbreak surveillance and comprehensive data documentation. Augmenting surveillance and embracing advancements in molecular/genomic characterisation techniques are crucial to precisely discerning DEC's actual impact and resistance continuum in Africa.Item Detection of the epidemic Pseudomonas aeruginosa AUST-03 (ST242) strain in people with cystic fibrosis in South Africa(Wiley, 2024-12) Hamiwe, Thabo; White, Debbie A.; Kwenda, Stanford; Ismail, Arshad; Klugman, Susan; Van Bruwaene, Lore; Goga, Ameena Ebrahim; Kock, Marleen M.; Smith, Anthony Marius; Ehlers, Marthie Magdaleen; marthie.ehlers@up.ac.zaINTRODUCTION: Pseudomonas aeruginosa AUST-03 (ST242) has been reported to cause epidemics in people with CF (pwCF) from Australia and has been associated with multidrug resistance and increased morbidity and mortality. Here, we report an epidemic P. aeruginosa (AUST-03) strain in South African pwCF detected at a public hospital and characterize the genomic antibiotic resistance determinants. METHODS: The P. aeruginosa AUST-03 (ST242) study isolates were analysed with whole genome sequencing using the Illumina NextSeq2000 platform. Raw sequencing reads were processed using the Jekesa pipeline and multilocus sequence typing and genomic antibiotic resistance characterization was performed using public databases. Genetic relatedness between the study isolates and global P. aeruginosa ST242 from public databases was determined using a maximum-likelihood phylogenetic tree. Antibiotic susceptibility testing was performed using the disk diffusion and broth microdilution techniques. RESULTS: A total of 11 P. aeruginosa AUST-03 isolates were isolated from two children with CF. The majority (8/11) of these isolates were multidrug-resistant (MDR) or extensively drug resistant; and the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM were the most clinically relevant antibiotic resistance determinants and were detected in all of the isolates. The study isolates were the most closely related to a 2020 P. aeruginosa AUST-03 (ST242) CF isolate from Russia. CONCLUSION: Epidemic MDR P. aeruginosa strains are present at South African public CF clinics and need to be considered when implementing segregation and infection control strategies to prevent possible spread and outbreaks.Item In vitro evaluation of the binding activity of novel mouse IgG1 opsonic monoclonal antibodies to Mycobacterium tuberculosis and other selected mycobacterial species(Elsevier, 2024-05) Nyazema, Kudzai B.; Shey, Bong-Akee; Sei, Clara J.; Peters, Remco P.H.; Maningi, Nontuthuko Excellent; Fischer, Gerald W.; Fourie, P.B. (Petrus Bernardus)Antimicrobial resistance alongside other challenges in tuberculosis (TB) therapeutics have stirred renewed interest in host-directed interventions, including the role of antibodies as adjunct therapeutic agents. This study assessed the binding efficacy of two novel IgG1 opsonic monoclonal antibodies (MABs; GG9 & JG7) at 5, 10, and 25 μg/mL to live cultures of Mycobacterium tuberculosis, M. avium, M. bovis, M. fortuitum, M. intracellulare, and M. smegmatis American Type Culture Collection laboratory reference strains, as well as clinical susceptible, multidrug resistant, and extensively drug resistant M. tuberculosis strains using indirect enzyme-linked immunosorbent assays. These three MAB concentrations were selected from a range of concentrations used in previous optimization (binding and functional) assays. Both MABs bound to all mycobacterial species and sub-types tested, albeit to varying degrees. Statistically significant differences in MAB binding activity were observed when comparing the highest and lowest MAB concentrations (p < 0.05) for both MABs GG9 and JG7, irrespective of the M. tuberculosis resistance profile. Binding affinity increased with an increase in MAB concentration, and optimal binding was observed at 25 μg/mL. JG7 showed better binding activity than GG9. Both MABs also bound to five MOTT species, albeit at varied levels. This non-selective binding to different mycobacterial species suggests a potential role for GG9 and JG7 as adjunctive agents in anti-TB chemotherapy with the aim to enhance bacterial killing.Item Intricate interplay of CRISPR-Cas systems, anti-CRISPR proteins, and antimicrobial resistance genes in a globally successful multi-drug resistant Klebsiella pneumoniae clone(BMC, 2025-01) Jiang, Jianping; Cienfuegos-Galletd, Astrid V.; Long, Tengfei; Peirano, Gisele; Chu, Tingyu; Pitout, Johann D.D.; Kreiswirth, Barry N.; Chen, LiangBACKGROUND : Klebsiella pneumoniae is one of the most prevalent pathogens responsible for multiple infections in healthcare settings and the community. K. pneumoniae CG147, primarily including ST147 (the founder ST), ST273, and ST392, is one of the most globally successful MDR clone linked to various carbapenemases. METHODS : One hundred and one CG147 strains were sequenced and additional 911 publicly available CG147 genome sequences were included for analysis. The molecular epidemiology, population structure, and time phylogeny were investigated. The virulome, resistome, and mobilome were analyzed, and the recombination in the capsular region was studied. The CRISPR-Cas and anti-CRISPR were identified. The interplay between CRISPR-Cas, anti-CRISPR, and carbapenemase-encoding plasmids was analyzed and experimentally validated. RESULTS : We analyzed 1012 global CG147 genomes, with 80.4% encoding at least one carbapenemase (NDM [529/1012, 52.3%], OXA-48-like [182/1012, 17.7%], and KPC [105/1012, 10.4%]). Surprisingly, almost all CG147 strains (99.7%, 1009/1,012) harbor a chromosomal type I-E CRISPR-Cas system, with 41.8% (423/1012) containing an additional plasmid-borne type IV-A3 CRISPR-Cas system, and both target IncF plasmids, e.g., the most prevalent KPC-encoding pKpQIL-like plasmids. We found the presence of IV-A3 CRISPR-Cas system showed a negative correlation with the presence of KPC. Interestingly, a prophage-encoding anti-CRISPR AcrIE8.1 and a plasmid-borne anti-CRISPR AcrIE9.2 were detected in 40.1% (406/1012) and 54.2% (548/1012) of strains, respectively, which displayed positive correlations with the presence of a carbapenemase. Plasmid transfer experiments confirmed that the I-E and IV-A3 CRISPR-Cas systems significantly decreased (p < 0.001) KPC-encoding pKpQIL plasmid conjugation frequencies, while the AcrIE8.1 and AcrIE9.2 significantly increased (p < 0.001) pKpQIL conjugation frequencies and protected plasmids from elimination by CRISPR-Cas I-E system. CONCLUSIONS : Our results indicated a complex interplay between CRISPR-Cas, anti-CRISPR, and mobile genetic elements that shape the evolution of CG147. Our findings advance the understanding of multi-drug resistance mechanisms and will aid in preventing the emergence of future MDR clones.Item Sodium, potassium-adenosine triphosphatase as a potential target of the anti-tuberculosis agents, clofazimine and bedaquiline(MDPI, 2024-12-04) Mmakola, Khomotso Madimetsa Shelboy; Balmith, Marissa [; Steel, Helen C.; Said, Mohamed; Potjo, Moliehi; Van der Mescht, Mieke Adri; Hlatshwayo, Nomsa; Meyer, Pieter Willem Adriaan; Tintinger, Gregory Ronald; Anderson, Ronald; Cholo, Moloko C.Multidrug-resistant tuberculosis (MDR-TB) patients are treated with a standardised, short World Health Organization (WHO) regimen which includes clofazimine (CFZ) and bedaquiline (BDQ) antibiotics. These two antibiotics lead to the development of QT prolongation in patients, inhibiting potassium (K+) uptake by targeting the voltage-gated K+ (Kv)11.1 (hERG) channel of the cardiomyocytes (CMs). However, the involvement of these antibiotics to regulate other K+ transporters of the CMs, as potential mechanisms of QT prolongation, has not been explored. This study determined the effects of CFZ and BDQ on sodium, potassium–adenosine triphosphatase (Na+,K+-ATPase) activity of CMs using rat cardiomyocytes (RCMs). These cells were treated with varying concentrations of CFZ and BDQ individually and in combination (1.25–5 mg/L). Thereafter, Na+,K+-ATPase activity was determined, followed by intracellular adenosine triphosphate (ATP) quantification and cellular viability determination. Furthermore, molecular docking of antibiotics with Na+,K+-ATPase was determined. Both antibiotics demonstrated dose–response inhibition of Na+,K+-ATPase activity of the RCMs. The greatest inhibition was demonstrated by combinations of CFZ and BDQ, followed by BDQ alone and, lastly, CFZ. Neither antibiotic, either individually or in combination, demonstrated cytotoxicity. Molecular docking revealed an interaction of both antibiotics with Na+,K+-ATPase, with BDQ showing higher protein-binding affinity than CFZ. The inhibitory effects of CFZ and BDQ, individually and in combination, on the activity of Na+,K+-ATPase pump of the RCMs highlight the existence of additional mechanisms of QT prolongation by these antibiotics.Item Spiritual holy water sites in Ethiopia : unrecognized high-risk settings for transmission of pulmonary tuberculosis(Wiley-Hindawi, 2024-04-08) Reta, Melese Abate; Maningi, Nontuthuko Excellent; Wubetu, Gizachew Yismaw; Olorunju, Steve A.S.; Fourie, P.B. (Petrus Bernardus)Ethiopia is a high-tuberculosis (TB) burden country with 157 new cases per 100,000 people, with 23,800 TB-related deaths in 2020. In Ethiopia, TB patients have different healthcare-seeking behaviors. They frequently visit spiritual places, such as holy water sites (HWSs), to seek treatment for their illness spiritually. This study examined the prevalence of pulmonary TB (PTB) and drug susceptibility profiles of Mycobacterium tuberculosis (MTB) isolates among spiritual HWS attendees in Northwest Ethiopia. A cross-sectional study was conducted from June 2019 to March 2020. Sputum samples were collected, processed, and cultured using Löwenstein-Jensen (LJ) culture medium. Second-generation line probe assays (LPAs), GenoType®MTBDRplus VER2.0 and GenoType®MTBDRsl VER2.0, were used to detect anti-TB drug-resistant isolates. STATA 17 was utilized to perform descriptive statistics, bivariate, and multivariate regression analyses. Of 560 PTB-symptomatic participants, 21.8% ((95% confidence interval (95 CI): 18.4-25.2%)) were culture-positive, resulting in a point prevalence of 1,183/100,000 attendees. Amongst HWS attendees, culture-positive TB occurred most commonly in persons 18-33 years of age (28.5% (95 CI 23.4-34.3%)). Other participant characteristics significantly associated with culture-positive PTB were as follows: rural residents (adjusted odds ratio (aOR) 2.65; 95 CI 1.38-5.10), married participants (aOR 2.43; 95 CI 1.28-4.63), family members >5 per household (aOR 1.84; 95 CI 1.04-3.24), and sharing living space (aOR 10.57; 95 CI 3.60-31.13). Also, among 438 participants followed for 12 months after showing negative TB culture results while at the HWS, 6.8% (95 CI 4.4-9.4%) developed or contracted culture-positive TB post-residency at the HWSs. Of the 122 tested isolates, 20 (16.4%) were isoniazid (INH) and/or rifampicin (RIF) resistant. Multidrug-resistant (MDR) TB was detected in 15 cases (12.3%), five of which were fluoroquinolones (FLQs) resistant. The findings from this study should raise a concern about HWSs as potential high-risk settings for TB transmission. It is recommended that appropriate control measures be instituted that include compulsory TB testing and tightened infection control at HWSs, where an increased risk exists for transmission of TB.Item Genetic diversity of Mycobacterium tuberculosis strains isolated from spiritual holy water site attendees in Northwest Ethiopia : a cross-sectional study(Elsevier, 2024-06) Reta, Melese Abate; Said, Halima M.; Maningi, Nontuthuko Excellent; Wubetu, Gizachew Yismaw; Agonafir, Mulualem; Fourie, P.B. (Petrus Bernardus); u18296603@tuks.co.zaBACKGROUND : The genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. METHODS : A cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the L¨owenstein- Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect firstand second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. RESULTS : Of 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East- African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/ CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%. Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. CONCLUSIONS : Diverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.Item Clostridioides difficile hypervirulent strain ST1 isolated from clinical stool specimens obtained from three Provinces in South Africa(Elsevier, 2025-02) Shirinda, Hlambani; Smith, Anthony Marius; Prinsloo, Ben; Kock, Marleen M.; Moodley, Mishalan; Ehlers, Marthie Magdaleen; marthie.ehlers@up.ac.zaPlease read abstract in the article.Item CRISPR-Cas9-mediated IncF plasmid curing in extraintestinal pathogenic Escherichia coli(American Society for Microbiology, 2024-01) Chen, Liang; Peirano, G.; Yen, Kelly; Wang, Bingjie; Terlecky, Austin; DeVinney, Rebekah; Kreiswirth, Barry N.; Pitout, Johann D.D.IncF plasmids are commonly found in extra-intestinal pathogenic Escherichia coli (ExPEC) strains, serving as reservoirs for antimicrobial resistance (AMR) genes and virulence factors, persistently coexisting with ExPEC lineages. Multidrug-resistant (MDR) high-risk ExPEC clones, particularly ST131, ST1193, and ST410, have acquired diverse IncF plasmids over time, containing various AMR determinants, contributing significantly to their global success. However, the broader roles of these IncF plasmids in the success of MDR ExPEC clones, beyond AMR, remain elusive. In this study, we employed a novel clustered regularly interspaced short palindromic repeats–CRISPR-associated protein-9 nuclease (CRISPR-Cas9)-mediated pCasCure plasmid-curing system to precisely remove specific IncF plasmids among ExPEC clones (ST1193, ST131, and ST410). Antibiotic-resistant parent strains reverted to antibiotic-susceptible states post-curing; however, IncF plasmid curing did not show significant impact on bacterial in vitro growth and had little impact on other in vitro phenotypes, including survival in water, dry environment and biofilm production. In addition, IncF plasmid curing did not affect the conjugation frequency of KPC-producing pKpQIL plasmid. This study represents a pivotal initial step in understanding the precise roles of IncF plasmids in the success of ExPEC. Future research will be crucial in investigating their influence on cell invasion and in vivo fitness, thereby providing a more comprehensive perspective on the functions of IncF plasmids in MDR ExPEC clones. IMPORTANCE : Understanding the role of IncF plasmids in the success of drug-resistant bacteria has far-reaching implications for tackling antibiotic resistance. The study's use of a novel CRISPR-Cas9-mediated plasmid-curing system provides a precision tool for dissecting the specific impact of IncF plasmids on ExPEC clones, especially high-risk, multidrug-resistant strains like ST131, ST1193, and ST410. The study offers a crucial stepping stone for future research into understanding how these plasmids influenceinfluenceinfluencemore complex aspects of bacterial behavior, such as cell invasion and in vivo fitness.Item Prevalence of intestinal parasitic infections and associated factors among food handlers in East Africa : a systematic review and meta-analysis(Springer, 2025-01) Ashagre, Agenagnew; Misganaw, Tadesse; Abebe, Wagaw; Dejazmach, Zelalem; Amare, Gashaw Azanaw; Wondmagegn, Yenesew Mihret; Worku, Kassahun Misgana; Adugna, Adane; Ahmed, Hassen; Gedifie, Solomon; Kumie, Getinet; Nigatie, Marye; Jemal, Abdu; Kasahun, Woldeteklehaimanot; Ayana, Sisay; Asmare, Zelalem; Gashaw, Yalewayker; Getachew, Ermias; Gashaw, Muluken; Sisay, Assefa; Tadesse, Selamyhun; Abate, Biruk Beletew; Kidie, Atitegeb Abera; Reta, Melesse AbateBACKGROUND : Intestinal parasitic infections are a significant public health concern, especially among food handlers, who can transmit these infections to the public through food preparation and handling. This systematic review and meta-analysis aimed to determine the pooled prevalence and associated factors of intestinal parasitic infections among food handlers in the East African region. METHODS : A systematic review and meta-analysis on intestinal parasitic infections among food handlers involved a comprehensive search across various databases, including Scopus, PubMed, ScienceDirect, Google Scholar, and the institution’s library registers. Forty relevant articles were identified and analyzed using STATA Software version 17.0. Sensitivity analysis, publication bias assessment with Egger’s test, and the Trim-and-fill meta-analysis for bias adjustment were conducted. Heterogeneity across the studies was assessed using Cochran’s Q statistic and I2 statistics, and subgroup analysis computed for significant heterogeneity (I2 value ≥ 50%). A random effect model was used to determine the pooled prevalence of intestinal parasitic infections. RESULTS : The pooled prevalence of intestinal parasitic infections among food handlers was 32.27% (95% CI 27.90–36.65). The most prevalent parasites were Entamoeba histolytica/dispar 20.83% (95% CI 13.66–28%), Ascaris lumbricoides 13.84% (95% CI 10–17.68%), Giardia lamblia 8.55% (95% CI 6.03–11.06%), and hookworm 6.43% (95% CI 3.93–8.93%). Using a common knife for cutting raw meat (AOR = 2.27, 95% CI 1.21–4.31), food handler’s untrimmed fingernails (AOR = 2.14, 95% CI 1.50–2.78), and no hand washing practices with soap after using the toilet (AOR = 2.25, 95% CI 1.33–3.18) were associated with higher rates of intestinal parasitic infections among food handlers. CONCLUSIONS : Parasitic infections among food handlers were found to be significantly prevalent. Factors contributing to this high prevalence included food handlers’ untrimmed fingernails, poor hand hygiene practices, and using a shared knife for chopping various food items, including raw meat. These findings emphasize the need for proper personal hygiene and sanitation practices among food handlers to prevent transmitting parasitic infections to consumers.Item Genomics sequence data of a drug-resistant Pseudomonas aeruginosa producing Tripoli Metallo-β-lactamase 1 isolated from Sudan(Elsevier, 2024-12) Mohammed, Sara E.; Hamid, Omnia; Abdelrahim, Mohammed; Ismail, Arshad; Smith, Anthony Marius; Allam, MushalPlease read abstract in article.Item Molecular epidemiology of multidrug-resistant Klebsiella pneumoniae, Enterobacter cloacae, and Escherichia coli outbreak among neonates in Tembisa hospital, South Africa(Frontiers Media, 2024-02) Osei Sekyere, John; Mmatli, Masego; Bosch, Anel; Ntsoane, Ramathetje V.; Naidoo, Harishia; Doyisa, Sinenhlanhla; Maningi, Nontuthuko Excellent; Mbelle, Nontombi Marylucy; Said, Mohamed; j.oseisekyere@up.ac.zaBACKGROUND: An outbreak of multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae infections in a neonatal ward within a tertiary hospital in South Africa resulted in the mortality of 10 patients within six months. In this work, the genomic epidemiology of and the molecular factors mediating this outbreak were investigated. METHODS: Bacterial cultures obtained from clinical samples collected from the infected neonates underwent phenotypic and molecular analyses to determine their species, sensitivity to antibiotics, production of carbapenemases, complete resistance genes profile, clonality, epidemiology, and evolutionary relationships. Mobile genetic elements flanking the resistance genes and facilitating their spread were also characterized. RESULTS: The outbreak was centered in two major wards and affected mainly neonates between September 2019 and March 2020. Most isolates (n = 27 isolates) were K. pneumoniae while both E. coli and E. cloacae had three isolates each. Notably, 33/34 isolates were multidrug resistant (MDR), with 30 being resistant to at least four drug classes. All the isolates were carbapenemasepositive, but four blaOXA-48 isolates were susceptible to carbapenems. BlaNDM-1 (n = 13) and blaOXA-48/181 (n = 15) were respectively found on IS91 and IS6-like IS26 composite transposons in the isolates alongside several other resistance genes. The repertoire of resistance and virulence genes, insertion sequences, and plasmid replicon types in the strains explains their virulence, resistance, and quick dissemination among the neonates. CONCLUSIONS: The outbreak of fatal MDR infections in the neonatal wards were mediated by clonal (vertical) and horizontal (plasmid-mediated) spread of resistant and virulent strains (and genes) that have been also circulating locally and globally.Item Editorial : Molecular mechanisms of resistance to “last resort” antimicrobials in Enterobacterales(Frontiers Media, 2024-05) Osei Sekyere, John; Schneiders, Thamarai; Majewski, Piotr; j.oseisekyere@up.ac.zaNo abstract available.Item True and false positive HIV point of care test results in a prospective multinational study of at-risk African women : implications for large-scale repeat HIV testing in HIV prevention programs(Wolters Kluwer Health, 2024-12) Morrison, Susan; Batting, Joanne; Wanga, Valentine; Beesham, Ivana; Deese, Jennifer; Hofmeyr, G. Justus; Kasaro, Margaret P.; Louw, Cheryl; Morrison, Charles; Mugo, Nelly R.; Palanee-Phillips, Thesla; Pleaner, Melanie; Reddy, Krishnaveni; Scoville, Caitlin W.; Smit, Jenni; Stringer, Jeffrey S.A.; Ahmed, Khatija; Bukusi, Elizabeth; Kotze, Philip; Baeten, Jared M.BACKGROUND : Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, although false (both negative and positive) results are expected to occur. SETTING : We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using 3 contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. METHODS : HIV serologic testing was conducted quarterly using 2 parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and RNA. RESULTS : A total of 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (ie, 1 negative and 1 positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing, but 6 (9.7%) had dually positive rapid results, and 4 (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. CONCLUSIONS : Although most rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low. TRIAL REGISTRATION : ClinicalTrials.gov number NCT02550067.Item Escherichia coli sequence type 410 with carbapenemases : a paradigm shift within E. coli toward multidrug resistance(American Society for Microbiology, 2024-02) Pitout, Johann D.D.; Peirano, Gisele; Matsumura, Yasufumi; DeVinney, Rebekah; Chen, LiangEscherichia coli sequence type ST410 is an emerging carbapenemase-producing multidrug-resistant (MDR) high-risk One-Health clone with the potential to significantly increase carbapenem resistance among E. coli. ST410 belongs to two clades (ST410-A and ST410-B) and three subclades (ST410-B1, ST410-B2, and ST410-B3). After a fimH switch between clades ST410-A and ST410-B1, ST410-B2 and ST410-B3 subclades showed a stepwise progression toward developing MDR. (i) ST410-B2 initially acquired fluoroquinolone resistance (via homologous recombination) in the 1980s. (ii) ST410-B2 then obtained CMY-2, CTX-M-15, and OXA-181 genes on different plasmid platforms during the 1990s. (iii) This was followed by the chromosomal integration of blaCMY-2, fstl YRIN insertion, and ompC/ompF mutations during the 2000s to create the ST410- B3 subclade. (iv) An IncF plasmid “replacement” scenario happened when ST410-B2 transformed into ST410-B3: F36:31:A4:B1 plasmids were replaced by F1:A1:B49 plasmids (both containing blaCTX-M-15) followed by blaNDM-5 incorporation during the 2010s. User-friendly cost-effective methods for the rapid identification of ST410 isolates and clades are needed because limited data are available about the frequencies and global distribution of ST410 clades. Basic mechanistic, evolutionary, surveillance, and clinical studies are urgently required to investigate the success of ST410 (including the ability to acquire successive MDR determinants). Such information will aid with management and prevention strategies to curb the spread of carbapenem-resistant E. coli. The medical community can ill afford to ignore the spread of a global E. coli clone with the potential to end the carbapenem era.Item Southern African HIV Clinicians Society guideline for the clinical management of syphilis(AOSIS, 2024-04-30) Peters, Remco P.H.; Nel, Jeremy; Sadiq, Eitzaz; Kufa, Tendesayi; Smit, Derrick P.; Sorour, Gillian; Garrett, Nigel; Gill, Katherine; Makhakhe, Lehlohonolo; Chandiwana, Nomathemba C.; Moran, Neil F.; Cohen, Karen; Wattrus, Camilla; Moosa, Mahomed YunusSyphilis, ‘the great imitator’, caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.Item Occurrence and characterization of ESKAPE organisms on the hands of veterinary students before patient contact at a veterinary academic hospital, South Africa(BMC, 2024-10) Sebola, Dikeledi; Oguttu, James Wabwire; Malahlela, M.N. (Mogaugedi); Kock, Marleen M.; Qekwana, Daniel NeneneOBJECTIVE: This study aimed to investigate the presence of ESKAPE organisms on the hands of students working in the intensive care unit (ICU) at a veterinary academic hospital. METHODS: A cross-sectional study was conducted among students working in an ICU at a veterinary academic hospital in South Africa. Students were sampled before the start of the ICU shift using a modified glove-juice method. Standard microbiological techniques and a series of polymerase chain reaction (PCR) assays were used to identify and characterize the bacteria. All the isolates were tested for resistance against a specific panel of antibiotics using the disk diffusion method. Proportions of bacterial species and their antimicrobial-susceptibility profiles were calculated. RESULTS: At screening, all the veterinary students (n=62) carried at least one of the ESKAPE organisms on their hands. Escherichia coli was the most isolated organism (76%, 47/62), followed by P. aeruginosa (48%, 30/62), A. baumannii (47%, 29/62), E. faecium (35%, 22/62), K. pneumoniae (27%, 17/62), and S. aureus (24%, 15/62). A reduced proportion of isolates were recovered from the samples, E. coli (26%, 12/47), E. faecium (23%, 5/22), P. aeruginosa (43%, 13/30), A. baumannii (24%,7/29), K. pneumoniae (41%, 7/17), and S. aureus (20%, 3/15). Most of the organisms showed a high proportion of resistance to at least one antibiotic. Multidrug resistance was reported among just over half (56%, 5/9) of E. coli, 40% (2/5) of E. faecium, 100% (13/13) of P. aeruginosa, and 33% (1/3) of S. aureus isolates. CONCLUSION: Students working in the ICU carry several organisms belonging to the ESKAPE group of organisms before contact with patients. Moreover, MDR resistance was common among this group of organisms. The findings of the present study underscore the importance of infection prevention and control (IPC) strategies to help reduce the likelihood of the spread of these organisms to personnel, owners, family members, and patients.Item Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives(Public Library of Science, 2023-11-10) Harryparsad, Rushil; Meyer, Bahiah; Taku, Ongeziwe; Serrano, Myrna; Chen, Pai Lien; Gao, Xiaoming; Williamson, Anna-Lise; Mehou-Loko, Celia; D’Hellencourt, Florence Lefebvre; Smit, Jennifer; Strauss, Jerome; Nanda, Kavita; Ahmed, Khatija; Beksinska, Mags; Buck, Gregory; Morrison, Charles; Deese, Jennifer; Masson, LindiBACKGROUND : South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. METHODS : We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18–33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. RESULTS : There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups– 18–21 years (46%), 22–25 years (42%) and 26–33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18–21 years) more likely to acquire CT (75.9/100 wy) compared to 26–33 year olds (17.4/ 100 wy; p = 0.049). TV incidence was higher in the 26–33 year old group (82.7/100 wy) compared to the 18–21 year olds (8.4/100 wy; p = 0.01). CONCLUSIONS : Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.